tbuckley/cabot-search huggingface dataset:
NCCN Guidelines® Insights: Prostate Cancer Early Detection, Version 1.2023
Authors: Kelvin A. Moses, Preston C. Sprenkle, Clinton Bahler, Geoffrey Box, Sigrid V. Carlsson, William J. Catalona, Douglas M. Dahl, Marc Dall’Era, John W. Davis, Bettina F. Drake, Jonathan I. Epstein, Ruth B. Etzioni, Thomas A. Farrington, Isla P. Garraway, David Jarrard, Eric Kauffman, Deborah Kaye, Adam S. Kibel, Chad A. LaGrange, Paul Maroni, Lee Ponsky, Brian Reys, Simpa S. Salami, Alejandro Sanchez, Tyler M. Seibert, Terrence M. Shaneyfelt, Marc C. Smaldone, Geoffrey Sonn, Mark D. Tyson, Neha Vapiwala, Robert Wake, Samuel Washington, Alice Yu, Bertram Yuh, Ryan A. Berardi, Deborah A. Freedman-Cass
Journal: Journal of the National Comprehensive Cancer Network (2023)

The NCCN Guidelines for Prostate Cancer Early Detection provide recommendations for individuals with a prostate who opt to participate in an early detection program after receiving the appropriate counseling on the pros and cons. These NCCN Guidelines Insights provide a summary of recent updates to the NCCN Guidelines with regard to the testing protocol, use of multiparametric MRI, and management of negative biopsy results to optimize the detection of clinically significant prostate cancer and minimize the detection of indolent disease.
Phase II Clinical Trial of Axitinib and Avelumab in Patients With Recurrent/Metastatic Adenoid Cystic Carcinoma
Authors: Renata Ferrarotto, Luana G. Sousa, Lei Feng, Frank Mott, George Blumenschein, Mehmet Altan, Diana Bell, Flavia Bonini, Kaiyi Li, Mario L. Marques-Piubelli, Eduardo A. Dal Lago, Jason J. Johnson, Yoshitsugu Mitani, Myrna Godoy, Anna Lee, Michael Kupferman, Ehab Hanna, Bonnie S. Glisson, Yasir Elamin, Adel El-Naggar
Journal: Journal of Clinical Oncology (2023)

We conducted a phase II trial evaluating the efficacy of VEGFR inhibitor axitinib and PD-L1 inhibitor avelumab in patients with recurrent/metastatic adenoid cystic carcinoma (R/M ACC).
An XBP1s–PIM-2 positive feedback loop controls IL-15–mediated survival of natural killer cells
Authors: Shoubao Ma, Jingjing Han, Zhenlong Li, Sai Xiao, Jianying Zhang, Jiazhuo Yan, Tingting Tang, Tasha Barr, Andrew S. Kraft, Michael A. Caligiuri, Jianhua Yu
Journal: Science Immunology (2023)

Spliced X-box-binding protein 1 (XBP1s) is an essential transcription factor downstream of interleukin-15 (IL-15) and AKT signaling, which controls cell survival and effector functions of human natural killer (NK) cells. However, the precise mechanisms, especially the downstream targets of XBP1s, remain unknown. In this study, by using XBP1 conditional knockout mice, we found that XBP1s is critical for IL-15-mediated NK cell survival but not proliferation in vitro and in vivo. Mechanistically, XBP1s regulates homeostatic NK cell survival by targeting PIM-2, a critical anti-apoptotic gene, which in turn stabilizes XBP1s protein by phosphorylating it at Thr58. In addition, XBP1s enhances the effector functions and antitumor immunity of NK cells by recruiting T-bet to the promoter region of Ifng. Collectively, our findings identify a previously unknown mechanism by which IL-15-XBP1s signaling regulates the survival and effector functions of NK cells.
Recent Advances on Cell Culture Platforms for In Vitro Drug Screening and Cell Therapies: From Conventional to Microfluidic Strategies
Authors: Beatriz D. Cardoso, Elisabete M. S. Castanheira, Senentxu Lanceros‐Méndez, Vanessa F. Cardoso
Journal: Advanced Healthcare Materials (2023)

Abstract The clinical translations of drugs and nanomedicines depend on coherent pharmaceutical research based on biologically accurate screening approaches. Since establishing the 2D in vitro cell culture method, the scientific community has improved cell‐based drug screening assays and models. Those advances result in more informative biochemical assays and the development of 3D multicellular models to describe the biological complexity better and enhance the simulation of the in vivo microenvironment. Despite the overall dominance of conventional 2D and 3D cell macroscopic culture methods, they present physicochemical and operational challenges that impair the scale‐up of drug screening by not allowing a high parallelization, multidrug combination, and high‐throughput screening. Their combination and complementarity with microfluidic platforms enable the development of microfluidics‐based cell culture platforms with unequivocal advantages in drug screening and cell therapies. Thus, this review presents an updated and consolidated view of cell culture miniaturization's physical, chemical, and operational considerations in the pharmaceutical research scenario. It clarifies advances in the field using gradient‐based microfluidics, droplet‐based microfluidics, printed‐based microfluidics, digital‐based microfluidics, SlipChip, and paper‐based microfluidics. Finally, it presents a comparative analysis of the performance of cell‐based methods in life research and development to achieve increased precision in the drug screening process.
Traction Bronchiectasis/Bronchiolectasis in Interstitial Lung Abnormality: Follow-up in the COPDGene Study
Authors: Akinori Hata, Takuya Hino, Yi Li, Takeshi Johkoh, David C. Christiani, David A. Lynch, Michael H. Cho, Edwin K. Silverman, Gary M. Hunninghake, Hiroto Hatabu
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Traction Bronchiectasis/Bronchiolectasis in Interstitial Lung Abnormality: Follow-up in the COPDGene Study." American Journal of Respiratory and Critical Care Medicine, 207(10), pp. 1395–1398
Bridging rapid and sustained antidepressant effects of ketamine
Authors: Ji-Woon Kim, Kanzo Suzuki, Ege T. Kavalali, Lisa M. Monteggia
Journal: Trends in Molecular Medicine (2023)

Acute administration of (R,S)-ketamine (ketamine) produces rapid antidepressant effects that in some patients can be sustained for several days to more than a week. Ketamine blocks N-methyl-d-asparate (NMDA) receptors (NMDARs) to elicit specific downstream signaling that induces a novel form of synaptic plasticity in the hippocampus that has been linked to the rapid antidepressant action. These signaling events lead to subsequent downstream transcriptional changes that are involved in the sustained antidepressant effects. Here we review how ketamine triggers this intracellular signaling pathway to mediate synaptic plasticity which underlies the rapid antidepressant effects and links it to downstream signaling and the sustained antidepressant effects.
How I treat erythropoietic protoporphyria and X-linked protoporphyria
Authors: Rebecca Karp Leaf, Amy K. Dickey
Journal: Blood (2023)

Erythropoietic protoporphyria (EPP) is an inherited cutaneous porphyria caused by reduced expression of ferrochelatase, the enzyme that catalyzes the final step in heme biosynthesis. The resultant accumulation of protoporphyrin IX leads to severe painful cutaneous photosensitivity, as well as potentially life-threatening liver disease in a small percentage of patients. X-linked protoporphyria (XLP) is similar to EPP clinically, but results from increased activity of δ-aminolevulinic acid synthase 2 (ALAS2), the first step in heme biosynthesis in the bone marrow, and also causes protoporphyrin accumulation. Although historically the management of EPP and XLP (collectively termed protoporphyria) centered around avoidance of sunlight, novel therapies have recently been approved or are in development, which will alter the therapeutic landscape for these conditions. We present three patient vignettes highlighting key treatment considerations in patients with protoporphyria including (1) approach to photosensitivity, (2) managing iron deficiency in protoporphyria, and (3) understanding hepatic failure in protoporphyria.
Effect of monthly intermittent preventive treatment with dihydroartemisinin–piperaquine with and without azithromycin versus monthly sulfadoxine–pyrimethamine on adverse pregnancy outcomes in Africa: a double-blind randomised, partly placebo-controlled trial
Authors: Mwayiwawo Madanitsa, Hellen C Barsosio, Daniel T R Minja, George Mtove, Reginald A Kavishe, James Dodd, Queen Saidi, Eric D Onyango, Kephas Otieno, Duolao Wang, Ulla Ashorn, Jenny Hill, Crispin Mukerebe, Samwel Gesase, Omari A Msemo, Victor Mwapasa, Kamija S Phiri, Kenneth Maleta, Nigel Klein, Pascal Magnussen, John P A Lusingu, Simon Kariuki, Jacklin F Mosha, Michael Alifrangis, Helle Hansson, Christentze Schmiegelow, Julie R Gutman, R Matthew Chico, Feiko O ter Kuile
Journal: The Lancet (2023)
Tumor microenvironment contribution to checkpoint blockade therapy. Lessons learned from Hodgkin lymphoma
Authors: Antonino Carbone, Annunziata Gloghini, Carmelo Carlo Stella
Journal: Blood (2023)

Classic Hodgkin lymphoma (cHL) is characterized by a tumor microenvironment (TME) containing inflammatory/immune cells. Follicular lymphoma, mediastinal grey zone lymphoma and diffuse large B-cell lymphomas, may show a TME containing inflammatory/immune cells, but the TMEs are quite different. In these B-cell lymphomas and cHL, PD-1/PD-L1 blockade drugs differ in their effectiveness in patients with refractory/relapsed disease. Research should still explore innovative assays that could reveal which molecules are influencing the sensitivity or the resistance to therapy in an individual patient.
When I use a word . . . . Data—usage and ownership
Authors: Jeffrey K Aronson
Journal: BMJ (2023)

Etymology, grammar, and usage all support the view that “data” not only is a plural noun but also should be used as such in most instances. However, perhaps under the influence of the way in which it is used in news media, general usage is drifting towards singular usage. Nevertheless, regarding “data” as a plural noun also informs the more difficult question of who owns the data (the individual items) or the database (the collection). It suggests that each individual owns his or her own [plural] data, when the data exist as discrete pieces of information about the individual—using the word “information” in the general, non-technical sense, outside its use in computer science. However, no one individual or institution owns an anonymised collection of data in a database or databank, although those who collected the data or paid to have them collected may have a legitimate preferential claim. Nevertheless it is reasonable to expect that collections of data should be shared and that communally everybody owns them, while respecting the anonymity of the individuals whose data are represented.
Long-term COVID-19 booster effectiveness by infection history and clinical vulnerability and immune imprinting: a retrospective population-based cohort study
Authors: Hiam Chemaitelly, Houssein H Ayoub, Patrick Tang, Peter Coyle, Hadi M Yassine, Asmaa A Al Thani, Hebah A Al-Khatib, Mohammad R Hasan, Zaina Al-Kanaani, Einas Al-Kuwari, Andrew Jeremijenko, Anvar Hassan Kaleeckal, Ali Nizar Latif, Riyazuddin Mohammad Shaik, Hanan F Abdul-Rahim, Gheyath K Nasrallah, Mohamed Ghaith Al-Kuwari, Adeel A Butt, Hamad Eid Al-Romaihi, Mohamed H Al-Thani, Abdullatif Al-Khal, Roberto Bertollini, Jeremy Samuel Faust, Laith J Abu-Raddad
Journal: The Lancet Infectious Diseases (2023)
Prospective Validation of the Prognostic Relevance of CD34+CD38- AML Stem Cell frequency in the HOVON-SAKK132 trial
Authors: Lok Lam Ngai, Diana Hanekamp, Fleur Janssen, Jannemieke Carbaat-Ham, Maaike A.M. Hofland, Mona M.H.E Fayed, Angèle Kelder, Laura Oudshoorn-van Marsbergen, Willemijn J. Scholten, Alexander N. Snel, Costa Bachas, Jesse M. Tettero, Dimitri A. Breems, Thomas Fischer, Bjorn T. Gjertsen, Laimonas Griskevicius, Gunnar Juliusson, Arjan A. van de Loosdrecht, Johan A. Maertens, Markus G. Manz, Thomas Pabst, Jakob R Passweg, Kimmo Porkka, Peter J.M. Valk, Patrycja Gradowska, Bob Löwenberg, David C. de Leeuw, Jeroen J.W.M. Janssen, Gert J. Ossenkoppele, Jacqueline Cloos
Journal: Blood (2023)
Level of pain catastrophising determines if patients with long-standing subacromial impingement benefit from more resistance exercise: predefined secondary analyses from a pragmatic randomised controlled trial (the SExSI Trial)
Authors: Mikkel Bek Clausen, Michael Skovdal Rathleff, Thomas Graven-Nielsen, Thomas Bandholm, Karl Bang Christensen, Per Hölmich, Kristian Thorborg
Journal: British Journal of Sports Medicine (2023)

The primary aim was to investigate the effectiveness of adding more resistance exercise to usual care on pain mechanisms (including temporal summation, conditioned pain modulation (CPM) and local pain sensitivity) and pain catastrophising in people with subacromial impingement at 16 weeks follow-up. Second, to investigate the modifying effect of pain mechanisms and pain catastrophising on the interventions' effectiveness in improving shoulder strength and disability METHODS: 200 consecutive patients were randomly allocated to usual exercise-based care or the same plus additional elastic band exercise to increase total exercise dose. Completed add-on exercise dose was captured using an elastic band sensor. Outcome measures recorded at baseline, 5 weeks, 10 weeks and 16 (primary end point) weeks included temporal summation of pain (TSP) and CPM assessed at the lower leg, pressure pain threshold at the deltoid muscle (PPT-deltoid), pain catastrophising and the Shoulder Pain and Disability Index.Additional elastic band exercise was not superior to usual exercise-based care in improving pain mechanisms (TSP, CPM and PPT-deltoid) or pain catastrophising after 16 weeks. Interaction analyses showed that pain catastrophising (median split) modified the effectiveness of additional exercises (effect size 14 points, 95% CI 2 to 25), with superior results in the additional exercise group compared with the usual care group in patients with less pain catastrophising.Additional resistance exercise added to usual care was not superior to usual care alone in improving pain mechanisms or pain catastrophising. Additional exercise was, however, superior in improving self-reported disability in patients with lower levels of pain catastrophising at baseline.NCT02747251.
Do biomechanical foot-based interventions reduce patellofemoral joint loads in adults with and without patellofemoral pain or osteoarthritis? A systematic review and meta-analysis
Authors: Samual A Kayll, Rana S Hinman, Adam L Bryant, Kim L Bennell, Patrick L Rowe, Kade L Paterson
Journal: British Journal of Sports Medicine (2023)

Objective To evaluate the effects of biomechanical foot-based interventions (eg, footwear, insoles, taping and bracing on the foot) on patellofemoral loads during walking, running or walking and running combined in adults with and without patellofemoral pain or osteoarthritis. Design Systematic review with meta-analysis. Data sources MEDLINE, CINAHL, SPORTdiscus, Embase and CENTRAL. Eligibility criteria for selecting studies English-language studies that assessed effects of biomechanical foot-based interventions on peak patellofemoral joint loads, quantified by patellofemoral joint pressure, reaction force or knee flexion moment during gait, in people with or without patellofemoral pain or osteoarthritis. Results We identified 22 footwear and 11 insole studies (participant n=578). Pooled analyses indicated low-certainty evidence that minimalist footwear leads to a small reduction in peak patellofemoral joint loads compared with conventional footwear during running only (standardised mean difference (SMD) (95% CI) = −0.40 (–0.68 to –0.11)). Low-certainty evidence indicated that medial support insoles do not alter patellofemoral joint loads during walking (SMD (95% CI) = −0.08 (–0.42 to 0.27)) or running (SMD (95% CI) = 0.11 (–0.17 to 0.39)). Very low-certainty evidence indicated rocker-soled shoes have no effect on patellofemoral joint loads during walking and running combined (SMD (95% CI) = 0.37) (−0.06 to 0.79)). Conclusion Minimalist footwear may reduce peak patellofemoral joint loads slightly compared with conventional footwear during running only. Medial support insoles may not alter patellofemoral joint loads during walking or running and the evidence is very uncertain about the effect of rocker-soled shoes during walking and running combined. Clinicians aiming to reduce patellofemoral joint loads during running in people with patellofemoral pain or osteoarthritis may consider minimalist footwear.
Microglia activation in the presence of intact blood–brain barrier and disruption of hippocampal neurogenesis via IL-6 and IL-18 mediate early diffuse neuropsychiatric lupus
Authors: Dionysis Nikolopoulos, Theodora Manolakou, Alexia Polissidis, Anastasia Filia, George Bertsias, Yassemi Koutmani, Dimitrios T Boumpas
Journal: Annals of the Rheumatic Diseases (2023)

Introduction Inflammatory mediators are detected in the cerebrospinal fluid of systemic lupus erythematosus patients with central nervous system involvement (NPSLE), yet the underlying cellular and molecular mechanisms leading to neuropsychiatric disease remain elusive. Methods We performed a comprehensive phenotyping of NZB/W-F1 lupus-prone mice including tests for depression, anxiety and cognition. Immunofluorescence, flow cytometry, RNA-sequencing, qPCR, cytokine quantification and blood–brain barrier (BBB) permeability assays were applied in hippocampal tissue obtained in both prenephritic (3-month-old) and nephritic (6-month-old) lupus mice and matched control strains. Healthy adult hippocampal neural stem cells (hiNSCs) were exposed ex vivo to exogenous inflammatory cytokines to assess their effects on proliferation and apoptosis. Results At the prenephritic stage, BBB is intact yet mice exhibit hippocampus-related behavioural deficits recapitulating the human diffuse neuropsychiatric disease. This phenotype is accounted by disrupted hippocampal neurogenesis with hiNSCs exhibiting increased proliferation combined with decreased differentiation and increased apoptosis in combination with microglia activation and increased secretion of proinflammatory cytokines and chemokines. Among these cytokines, IL-6 and IL-18 directly induce apoptosis of adult hiNSCs ex vivo. During the nephritic stage, BBB becomes disrupted which facilitates immune components of peripheral blood, particularly B-cells, to penetrate into the hippocampus further augmenting inflammation with locally increased levels of IL-6, IL-12, IL-18 and IL-23. Of note, an interferon gene signature was observed only at nephritic-stage. Conclusion An intact BBB with microglial activation disrupting the formation of new neurons within the hippocampus represent early events in NPSLE. Disturbances of the BBB and interferon signature are evident later in the course of the disease.
Do cardiopulmonary exercise tests predict summit success and acute mountain sickness? A prospective observational field study at extreme altitude
Authors: Thomas Seiler, Christos T Nakas, Anne-Kathrin Brill, Urs Hefti, Matthias Peter Hilty, Eveline Perret-Hoigné, Jannis Sailer, Hans-Joachim Kabitz, Tobias M Merz, Jacqueline Pichler Hefti
Journal: British Journal of Sports Medicine (2023)

Objective During a high-altitude expedition, the association of cardiopulmonary exercise testing (CPET) parameters with the risk of developing acute mountain sickness (AMS) and the chance of reaching the summit were investigated. Methods Thirty-nine subjects underwent maximal CPET at lowlands and during ascent to Mount Himlung Himal (7126 m) at 4844 m, before and after 12 days of acclimatisation, and at 6022 m. Daily records of Lake-Louise-Score (LLS) determined AMS. Participants were categorised as AMS+ if moderate to severe AMS occurred. Results Maximal oxygen uptake (V̇O 2max ) decreased by 40.5%±13.7% at 6022 m and improved after acclimatisation (all p&lt;0.001). Ventilation at maximal exercise (VE max ) was reduced at 6022 m, but higher VE max was related to summit success (p=0.031). In the 23 AMS+ subjects (mean LLS 7.4±2.4), a pronounced exercise-induced oxygen desaturation (ΔSpO 2exercise ) was found after arrival at 4844 m (p=0.005). ΔSpO 2exercise &gt;-14.0% identified 74% of participants correctly with a sensitivity of 70% and specificity of 81% for predicting moderate to severe AMS. All 15 summiteers showed higher V̇O 2max (p&lt;0.001), and a higher risk of AMS in non-summiteers was suggested but did not reach statistical significance (OR: 3.64 (95% CI: 0.78 to 17.58), p=0.057). V̇O 2max ≥49.0 mL/min/kg at lowlands and ≥35.0 mL/min/kg at 4844 m predicted summit success with a sensitivity of 46.7% and 53.3%, and specificity of 83.3% and 91.3%, respectively. Conclusion Summiteers were able to sustain higher VE max throughout the expedition. Baseline V̇O 2max below 49.0 mL/min/kg was associated with a high chance of 83.3% for summit failure, when climbing without supplemental oxygen. A pronounced drop of SpO 2exercise at 4844 m may identify climbers at higher risk of AMS.
Heterologous vaccination with subunit protein vaccine induces a superior neutralizing capacity against BA.4/5‐included SARS‐CoV‐2 variants than homologous vaccination of mRNA vaccine
Authors: Dandan Peng, Tingmei Zhao, Weiqi Hong, Minyang Fu, Cai He, Li Chen, Wenyan Ren, Hong Lei, Jingyun Yang, Aqu Alu, Yanghong Ni, Jian Liu, Jiong Li, Wei Wang, Guobo Shen, Zhiwei Zhao, Li Yang, Jinliang Yang, Zhenling Wang, Yoshimasa Tanaka, Guangwen Lu, Xiangrong Song, Xiawei Wei
Journal: MedComm (2023)

Abstract BA.4 and BA.5 (BA.4/5), the subvariants of Omicron, are more transmissible than BA.1 with more robust immune evasion capability because of its unique spike protein mutations. In light of such situation, the vaccination against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is in desperate need of the third booster. It has been reported that heterologous boosters might produce more effective immunity against wild‐type SARS‐CoV‐2 and the variants. Additionally, the third heterologous protein subunit booster should be considered potentially. In the present study, we prepared a Delta full‐length spike protein sequence‐based mRNA vaccine as the “priming” shot and developed a recombinant trimeric receptor‐binding domain (RBD) protein vaccine referred to as RBD–HR/trimer as a third heterologous booster. Compared to the homologous mRNA group, the heterologous group (RBD–HR/trimer vaccine primed with two mRNA vaccines) induced higher neutralizing antibody titers against BA.4/5‐included SARS‐CoV‐2 variants. In addition, heterologous vaccination exhibited stronger cellular immune response and long‐lasting memory response than the homologous mRNA vaccine. In conclusion, a third heterologous boosting with RBD–HR/trimer following two‐dose mRNA priming vaccination should be a superior strategy than a third homologous mRNA vaccine. The RBD–HR/trimer vaccine becomes an appropriate candidate for a booster immune injection.